Lysosomal Storage Disorders: Urine Screening

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Lysosomal Storage Disorders: Urine Screening Test Code: BLSDS Turnaround time: 2 weeks (GAGs performed Fri 10 am / Oligos performed Fri 3 pm) CPT Codes: 82542 x1, 82570 x1, 83864 x1, 84275 x1, 84375 x1, 84377 x1

Condition Description

Notice: This test has been discontinued

EGL no longer accepts samples for this test. For questions, please call: 470-378-2200

In glycoprotein storage diseases (GSDs), certain subtypes of congenital disorders of glycosylation (CDGs), and in the mucolipidoses, there is an accumulation of oligosaccharides, free glycans, glycoamino acids, glycolipid and glycopeptide in the urine. Glycoprotein storage diseases are genetic conditions caused by the body's inability to produce specific enzymes. Normally, the body uses enzymes to process, break down and recycle materials in cells. In individuals with GSD and related diseases, the missing or insufficient enzyme prevents the proper processing and recycling process. This results in the storage of materials, called oligosaccharides or free glycans and glycoamino acids in virtually every cell of the body. As a result, cells do not perform properly and may cause progressive damage throughout the body, including the heart, bones, joints, respiratory system, immune system and central nervous system.

While the disease may or may not be apparent at birth, signs and symptoms develop with age as more cells become damaged by the accumulation of materials. The symptoms of these diseases may vary based on syndrome type, and in some cases may resemble a mucopolysaccharidosis.

This urinary oligosaccharide and glycan screening uses mass spectrometry (MS), which provides a better sensitivity and specificity than traditional TLC methods. The MS method successfully detects subtle excretions of abnormal oligosaccharides in mucolipidosis II and III (I cell disease) as well as other oligosaccharidosis.

Conditions screened for include the following:

Alpha-mannosidosis Asparylglucosaminuria Beta-mannosidosis CDGIIb Fucosidosis Galactosialidosis GM1 Gangliosidosis GM2 (Tay Sachs/Sandhoff/GM2 activator deficiency) Kanzaki disease Mucolipidosis II and III (I cell disease) Pompe disease Schindler disease Sialidosis

Mucopolysaccharidoses (MPS) are genetic lysosomal storage diseases (LSDs) caused by the body's inability to produce specific enzymes. Normally, the body uses enzymes to break down and recycle materials in cells. In individuals with MPS and related diseases, the missing or insufficient enzyme prevents the proper recycling process. This results in the storage of materials, called glycosaminoglycans or GAGS, in virtually every cell of the body. As a result, cells do not perform properly and may cause progressive damage throughout the body, including the heart, bones, joints, respiratory system and central nervous system. While the disease may not be apparent at birth, signs and symptoms develop with age as more cells become damaged by the accumulation of materials.

While the symptoms may vary from one syndrome to another, there are many similarities. Affected individuals often have mental retardation, cloudy corneas, short stature, stiff joints, speech and hearing impairment, large liver and spleen, hernias, heart disease, hyperactivity, pain, and a dramatically shortened life span. Currently, there are six identified MPS conditions. Most are autosomal recessively inherited with the exception of Hunter syndrome (MPS II), which is X-linked recessively inherited.

MPS diseases include:

MPS type I (Hurler, Scheie, and Hurler-Scheie syndrome) MPS Type II (Hunter syndrome) MPS Type III (Sanfilippo Types A, B, C, and D) MPS Type IV (Morquio Types A and B) MPS Type VI (Maroteaux-Lamy syndrome) MPS Type VII (Sly syndrome)

Sialic acid storage diseases (SSDs) are severe autosomal recessive neurodegenerative disorders caused by a transport defect across the lysosomal membrane, which leads to accumulation of sialic acid in tissues, fibroblasts, and urine. Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, hypotonia, and failure to thrive. They may have coarse facial features, seizures, bone malformations, hepatosplenomegaly and cardiomegaly. The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid

Disclaimer: This information is confidential and subject to change without notice. It may not be reproduced in whole or part unless 09-23-2021 1 / 3 authorized in writing by an authorized EGL representative. 2460 Mountain Industrial Boulevard | Tucker, Georgia 30084 Phone: 470-378-2200 or 855-831-7447 | Fax: 470-378-2250 eglgenetics.com

accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.

Mutations in the SLC17A5 gene cause all forms of sialic acid storage disease. This gene provides instructions for producing a protein called sialin that is located mainly on the membranes of lysosomes, compartments in the cell that digest and recycle materials. Sialin moves free sialic acid, produced when glycoproteins or glycolipids are broken down, out of the lysosomes to other parts of the cell. Free sialic acid means that the sialic acid is not attached (bound) to other molecules. Elevated free sialic acid in urine is a useful first tier screening test for sialic acid storage disorders. Some cases may present with normal urine levels. In these individuals, determination of CSF sialic acid levels may be necessary.

In addition to sialic acid transporter disorder, urine free sialic acid levels could be elevated in a patient with sialuria, a rare autosomal dominant condition due to certain mutations in GNE gene. Indications

This test is indicated for:

Patients whose clinical evaluations are suggestive of glycoprotein storage diseases or mucopolysaccharidoses. Glycoprotein degradation defects. Multi-system disorders suggestive of congenital disorders of glycosylation, such as CDGIIb. Hydrops fetalis. Patients with severe developmental delay, coarse facial features, hepatosplenomegaly, cardiomegaly, prenatal or neonatal nonimmune hydrops, deterioration or loss of milestones in infancy, seizures, proteinuria, nephrotic syndrome, skeletal features, and hypotonia. Older patients with spasticity, epileptic seizures, and athetosis, abnormal myelination and white matter changes. Methodology

Oligosaccharides: The traditional one-dimensional thin-layer chromatography method for urine oliogsaccharides analysis has limited specificity and sensitivity and provides no structural information that is often needed for diagnoses. This test provides a sensitive screening method for structural analysis of urinary oligosaccharides, glycan and glycoamino acids by liquid chromatography-mass spectrometry using quadrupole - time of flight detection.

GAGS: Dimethylene Blue Binding Quantitation and Thin Layer Chromatography

Free sialic acid: HPLC-ESI-MS/MS. Free N-acetylneuraminic acid (Neu5Ac or NANA) is measured as the representative of sialic acid. Detection

This test provides a comprehensive tool for initial screening of lysosomal strorage disorders. The combination of urine oligosaccharide/free glycan and urine quantitative and fractionation of GAG's increases the sensitivity and specificity of urinary screening for lysosomal storage disorders. Urine oligosaccharide screening by mass spectrometry provides large amounts of information to identify abnormal species which can pinpoint a specific diagnosis more quickly than other assays. While the quantification and fractionation of glycosaminoglycans provides additional information that differentiates between the different types of mucopolysaccharidosis.

Abnormal results should be confirmed by enzyme and molecular analysis, as appropriate. Reference Range

Specimen Requirements

Submit only 1 of the following specimen types Type: Urine

Specimen Requirements: Clean container without additives 15-30 ml Freeze sample. Fasting or first void sample is preferable.

Specimen Collection and Shipping: Ship frozen sample on dry ice with overnight delivery. Special Instructions

Include the family history, clinical condition (asymptomatic or acute episode), diet and drug therapy information with the requisition. Related Tests

Lysosomal Enzyme Screen (LS) Mucopolysaccharide Screen (GA)

Disclaimer: This information is confidential and subject to change without notice. It may not be reproduced in whole or part unless 09-23-2021 2 / 3 authorized in writing by an authorized EGL representative. 2460 Mountain Industrial Boulevard | Tucker, Georgia 30084 Phone: 470-378-2200 or 855-831-7447 | Fax: 470-378-2250 eglgenetics.com

Oligosaccharide and Glycan Screening (OS) SSLC1: Free Sialic Acid Storage Disorders: SLC17A5 Gene Sequencing SGNEX: Congenital Disorder of Glycosylation, GNE-related: GNE Gene Sequencing DGNEX: Congenital Disorder of Glycosylation, GNE-related: GNE Gene Deletion/Duplication Custom Diagnostic Mutation Analysis (test code KM) - is available to individuals. Please contact the laboratory genetic counselor to arrange testing Prenatal testing may be available by molecular methods. Please contact the laboratory genetic counselor to determine the availability of prenatal testing

Molecular testing by sequencing and deletion/duplication is available at Emory Genetics Laboratory for most of the conditions identified by this test.

Disclaimer: This information is confidential and subject to change without notice. It may not be reproduced in whole or part unless 09-23-2021 3 / 3 authorized in writing by an authorized EGL representative.